This is a renewal application for a long-standing, highly focused training program that provides predoctoral and postdoctoral trainees with intensive research experience in the areas of synapses, ion channels, and transduction, while ensuring that the trainees have a thorough grounding in the basic neurosciences. The approaches involve the use of advanced molecular biological, physical, chemical, electrical, mathematical, and computational techniques to study fundamental questions in these focused areas of cellular and molecular neuroscience in which the 20 training faculty have expertise. Predoctoral trainees will enter the program after taking an interdisciplinary group of graduate courses and specialized courses tailored to their needs and interests. Under a mentor's direction they will do original research culminating in a Ph.D. degree. Postdoctoral trainees are offered a choice of research projects from which they develop their own independent research. All trainees receive much individual attention from program and allied faculty. Training involves a broad variety of research activities including presentations and participation in seminars and journal clubs with a large and closely interacting group of neuroscientists. The trainees also take part in career and ethics workshops and gain some teaching experience. The aim of this training program is to produce scientists of high quality, capable of working at the forefront of their research area, broadly knowledgeable in the basic neurosciences, and able to communicate effectively. The trainees will be qualified for diverse advanced positions in the biomedical sciences, ranging from the traditional academic to those in private industry and government. In keeping with the rigorous nature of the program, we seek first- rate applicants. Predoctoral candidates must be strong academically, with demonstrated interest in, and aptitude for, scientific inquiry. Postdoctoral candidates with Ph.D.s must have completed a high quality research project in a relevant discipline;individuals with M.D. degrees are actively recruited. Support is requested for 2 pre- and 2 postdoctoral trainees and short-term training for 4 medical students. The focused training forms the basis for understanding many diseases and disorders of the nervous system, including neurodegeneration, channelopathies, and dysfunction from genetic mutation. By training neuroscientists for research in these critical areas, the program is expected to contribute substantially to public health.